Not all kratom is equal: The important distinction between native leaf and extract products

Abstract

The Southeast Asian plant kratom (Mitragyna speciosa Korth.) has garnered growing popularity among North American consumers as a herbal product used for recreational, performance enhancement and self-treatment purposes. Scientifically, there has also been substantial interest in studying kratom and its constituents as a possible therapy for several conditions, including pain, mood, fatigue and substance use disorders (SUDs) [1]. Pre-clinical animal studies, human surveys and clinical case reports indicate that kratom has potential therapeutic effects as well as possible abuse and dependence potential, consistent with its complex opioidergic, adrenergic and serotonergic pharmacology [2]. Kratom is not federally recognized as a dietary supplement, and is therefore largely unregulated. Native kratom leaf material contains up to 2% of the major indole alkaloid mitragynine by weight. In addition, more than 50 other indole and oxindole alkaloids, some with known pharmacological effects, are present in lesser, but potentially significant, amounts [3]. Recently, there is a growing and concerning commercial trend in Western countries towards the production and marketing of kratom extract products created via extraction of kratom leaves using organic solvents. This enrichment process can increase the mitragynine concentration to 40% or higher in such products. Of great concern from a public health perspective, commercial kratom extract products lack data regarding their safety, efficacy and abuse potential. In addition, the formulation of concentrated kratom extracts as capsules, tablets, liquid shots or gummies circumvents kratom’s natural self-limiting qualities (e.g. unpleasant taste) and reduces the volume of product needed to achieve an effect, thereby raising the risk of users ingesting larger amounts of alkaloids with potentially toxic effects. History has shown us that developing enriched natural-product elixirs or purified active agents, as with cocaine from the coca shrub and morphine from the opium poppy, can be both a blessing and a curse: a blessing in that some of these concentrates can be medically useful to improve quality of life for patients suffering from a variety of disorders and a curse of increased risk. Concentrated kratom extracts are analogous to these previous historical examples. They may provide benefit to some, but they may result in unpredictable adverse effects and other potential harms resulting from dependence and drug–drug interactions. As researchers studying the therapeutic potential of kratom, while also desiring to reduce possible associated harms, we strongly recommend that kratom in its native form as the unadulterated fresh or dried leaf material remains available to consumers with proper oversight and regulation, including clear labeling describing the amount of mitragynine per dose, recommended maximum daily doses, potential for drug interactions and implementation of proper good manufacturing practices (GMP), similar to other dietary supplements. We also urge health-care providers to be open to discussing the potential use, drug interactions and risks of kratom with patients. Finally, consumers should be informed about the possible risks of regular or frequent use of concentrated kratom extract products that are formulated to expose users to much larger concentrations of kratom alkaloids than could be achieved with the native leaf material. Given the limited data on the risks and toxicity of concentrated kratom products, consumers should approach them with caution, and they should consult with their health-care provider before using any kratom product, including and especially kratom extracts. Oliver Grundmann: Conceptualization (lead); supervision (lead); writing—original draft (lead); writing—review and editing (equal). Albert Garcia-Romeu: Conceptualization (equal); writing—review and editing (equal). Christopher R. McCurdy: Conceptualization (equal); writing—review and editing (equal). Abhisheak Sharma: Conceptualization (equal); writing—review and editing (equal). Kirsten E. Smith: Conceptualization (equal); writing—original draft (equal); writing—review and editing (equal). Marc T. Swogger: Conceptualization (equal); writing—review and editing (equal). Stephanie T. Weiss: Conceptualization (equal); writing—review and editing (equal). This research received no specific grant from any funding agency in the public, commercial, or not-for-profit sectors. This work was supported in part by the Intramural Research Program of the National Institutes of Health, NIDA. The authors declare that there are no conflicts of interest.

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